Ursolisin
Italy
URSOLISIN 150 mg HARD CAPSULES
URSOLISIN 300 mg HARD CAPSULES
URSODESOXYCHOLIC ACID
COMPOSITION
URSOLISIN 150 mg hard capsules
Each capsule contains:
Active substance: Ursodesoxycholic acid 150 mg
Excipients: Maize starch, Sodium starch glycolate, Anhydrous colloidal silica, Magnesium stearate
Capsule shell composition: Highly purified gelatin, Titanium dioxide
URSOLISIN 300 mg hard capsules
Each capsule contains:
Active substance: Ursodesoxycholic acid 300 mg
Excipients: Maize starch, Sodium starch glycolate, Anhydrous colloidal silica, Magnesium stearate
Capsule shell composition: Highly purified gelatin, Titanium dioxide
PHARMACEUTICAL FORM AND CONTENT
150 mg hard capsules - 20 Capsules
150 mg hard capsules - 30 Capsules
150 mg hard capsules - 40 Capsules
300 mg hard capsules - 10 Capsules
300 mg hard capsules - 20 Capsules
300 mg hard capsules - 100 Capsules
Not all pack sizes may be marketed.
THERAPEUTIC CATEGORY
Hepatobiliary anti-lithogenic, litholytic agent.
MARKETING AUTHORISATION HOLDER
AESCULAPIUS FARMACEUTICI S.r.l. - Via Cefalonia, 70 - 25124 BRESCIA
MANUFACTURER AND FINAL CONTROLLER
ICE S.p.A. – Cantone Moretti, 29 - 10015 Ivrea (TO)
THERAPEUTIC INDICATIONS
Qualitative or quantitative disorders of bile production, including conditions with cholesterol-supersaturated bile, to prevent the formation of cholesterol stones or to create favorable conditions for the dissolution of existing radiolucent stones; in particular, gallbladder stones in a functioning gallbladder and residual or recurrent stones in the common bile duct following biliary tract surgery.
Biliary dyspepsia.
CONTRAINDICATIONS
Ursolisin must not be used in patients with:
- Acute inflammation of the gallbladder or biliary tract
- Biliary tract obstruction (common or cystic duct obstruction)
- Frequent episodes of biliary colic
- Calcified, radiopaque gallstones
- Impaired gallbladder contractility
- Hypersensitivity to bile acids or to any of the excipients
INTERACTIONS
Ursolisin must not be co-administered with cholestyramine, colestipol, or antacids containing aluminium hydroxide and/or smectite (aluminium oxide), as these substances bind ursodesoxycholic acid in the intestine and thereby inhibit its absorption and efficacy. If concomitant use of any of these agents is necessary, they should be taken at least 2 hours before or after Ursolisin.
Ursolisin may affect intestinal absorption of cyclosporine. Therefore, in patients receiving cyclosporine, blood concentrations should be monitored by the physician and the cyclosporine dose adjusted if necessary.
In isolated cases, Ursolisin may reduce the absorption of ciprofloxacin.
In a clinical study in healthy volunteers, concomitant use of ursodesoxycholic acid (500 mg/day) and rosuvastatin (20 mg/day) resulted in slightly increased plasma levels of rosuvastatin. The clinical relevance of this interaction, also regarding other statins, is unknown.
Ursodesoxycholic acid has been shown to reduce the peak plasma concentration (Cmax) and area under the curve (AUC) of the calcium antagonist nitrendipine in healthy volunteers. Careful monitoring is recommended when nitrendipine and ursodesoxycholic acid are used concomitantly. An increase in nitrendipine dosage may be necessary. An interaction resulting in reduced therapeutic effect of dapsone has also been reported. These observations, together with in vitro evidence, suggest a potential induction of cytochrome P450 3A enzymes by ursodesoxycholic acid.
However, no induction was observed in a well-designed interaction study with budesonide, a known substrate of cytochrome P450 3A.
Estrogen hormones and cholesterol-lowering agents such as clofibrate increase hepatic cholesterol secretion and may therefore promote gallstone formation, which opposes the action of ursodesoxycholic acid used for stone dissolution.
SPECIAL WARNINGS
Ursolisin must be taken under medical supervision.
During the first 3 months of treatment, liver function parameters AST (SGOT), ALT (SGPT), and γ-GT should be monitored by the physician every 4 weeks, and thereafter every 3 months.
In addition to identifying responders and non-responders in the treatment of primary biliary cirrhosis, this monitoring should also allow early detection of potential hepatic deterioration, particularly in patients with advanced-stage primary biliary cirrhosis.
When used for dissolution of cholesterol stones:
To confirm therapeutic improvement and timely identification of any stone calcification, depending on stone size, the gallbladder should be visualized (oral cholecystography) with overview and occluded duct views in upright and supine positions (ultrasound monitoring) 6–10 months after starting treatment.
Ursolisin must not be used if gallbladder visualization by X-ray imaging is not possible, or in case of calcified stones, impaired gallbladder contractility, or frequent episodes of biliary colic.
Female patients taking Ursolisin for stone dissolution must use an effective non-hormonal contraceptive method, as hormonal contraceptives may increase the risk of gallstone formation (see sections: “Interactions” and “Fertility, pregnancy and lactation”).
When used for the treatment of advanced-stage primary biliary cirrhosis:
In very rare cases, hepatic decompensation has been observed, which partially regressed after discontinuation of treatment.
In patients with PBC (primary biliary cirrhosis), clinical symptoms may rarely worsen at the beginning of treatment, for example, pruritus may increase. In such cases, the dose of ursodesoxycholic acid should be reduced to one 250 mg capsule daily and then gradually increased as described in the section “Dosage, method and duration of administration”.
If diarrhea occurs, the dose should be reduced; if diarrhea persists, treatment should be discontinued.
FERTILITY, PREGNANCY AND LACTATION
Animal studies have not shown any effect of ursodesoxycholic acid on fertility. Human data regarding effects on fertility following treatment with ursodesoxycholic acid are not available.
There are no or limited data on the use of ursodesoxycholic acid in pregnant women. Animal studies have shown reproductive toxicity during early gestation. Ursolisin must not be used during pregnancy unless clearly necessary.
Women of childbearing potential must only be treated if they use a reliable contraceptive method: non-hormonal contraceptives or low-estrogen oral contraceptives are recommended. However, in patients taking Ursolisin for cholesterol stone dissolution, an effective non-hormonal contraceptive method must be used, since hormonal oral contraceptives may increase the risk of biliary lithiasis. Pregnancy must be excluded before starting treatment.
Based on the few documented cases of breastfeeding women, levels of ursodesoxycholic acid in breast milk are very low and adverse reactions in breastfed infants are unlikely.
DRIVING AND USE OF MACHINES
Ursodesoxycholic acid does not impair or impairs negligibly the ability to drive vehicles or operate machinery.
DOSAGE, METHOD AND DURATION OF ADMINISTRATION
The availability of 150 mg and 300 mg strengths allows for flexible dosing regimens suitable for various clinical conditions.
For long-term use to reduce the lithogenic properties of bile, the usual daily dose is 5–10 mg/kg. In most cases, the daily dose ranges between 300 and 600 mg, equivalent to 2–4 capsules of 150 mg daily, or alternatively one 300 mg capsule twice daily (morning and evening). To maintain conditions favorable for dissolution of existing stones, treatment should last at least 4–6 months, up to 12 months or longer.
For biliary dyspepsia and maintenance therapy, doses of 150 mg once or twice daily are generally sufficient.
Dosages may be adjusted at the physician’s discretion; in particular, the excellent tolerability of the drug allows even significantly higher doses to be used.
Capsules should preferably be taken during or after meals.
OVERDOSE
In case of overdose, diarrhea may occur. Generally, other symptoms of overdose are unlikely, as absorption of ursodesoxycholic acid decreases with increasing dose, resulting in greater fecal excretion.
No specific antidotes are required. Consequences of diarrhea should be managed symptomatically with fluid and electrolyte replacement.
Additional information on special populations:
Long-term therapy with high-dose ursodesoxycholic acid (28–30 mg/kg/day) in patients with primary sclerosing cholangitis (an unauthorised, so-called off-label use) has been associated with higher rates of serious adverse events.
UNDESIRABLE EFFECTS
Like all medicines, Ursolisin can cause adverse effects, although not everyone experiences them.
Assessment of adverse effects is based on the following frequency categories:
Very common (≥ 1/10),
Common (≥ 1/100, < 1/10),
Uncommon (≥ 1/1000, < 1/100),
Rare (≥ 1/10000, < 1/1000),
Very rare/Not known (< 1/10000 / frequency cannot be estimated from available data).
Gastrointestinal disorders:
In clinical trials, soft stools or diarrhea during treatment with ursodesoxycholic acid have been commonly reported.
Very rarely, severe right upper quadrant abdominal pain has occurred during treatment of primary biliary cirrhosis.
Hepatobiliary disorders:
In very rare cases, calcification of gallstones may occur during treatment with ursodesoxycholic acid. During treatment of advanced-stage primary biliary cirrhosis, hepatic decompensation has been observed in very rare cases, which partially regressed after treatment discontinuation.
Skin and subcutaneous tissue disorders:
Very rarely, urticaria may occur.
Following the instructions provided in this leaflet reduces the risk of adverse effects.
If any of the adverse effects worsens, or if you notice any adverse effects not listed in this leaflet, inform your doctor or pharmacist.
REPORTING OF ADVERSE EFFECTS
If you experience any adverse effect, including those not listed in this leaflet, consult your doctor or pharmacist. Adverse effects can also be reported directly via the national reporting system at https://www.aifa.gov.it/en/content/segnalazioni-reazioni-avverse. Reporting adverse effects contributes to providing more information on the safety of this medicine.
EXPIRY DATE AND STORAGE
Expiry date: see the date printed on the packaging.
The expiry date refers to the product stored in its original unopened packaging under recommended conditions.
Do not use the medicine after the expiry date stated on the packaging.
No special storage precautions required.
KEEP THIS MEDICINE OUT OF THE SIGHT AND REACH OF CHILDREN.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.
REVISION OF THE PACKAGE LEAFLET BY THE ITALIAN MEDICINES AGENCY :